A certain population of pluripotent stem-cells residing in the bone-marrow of adult mammalians have the potential to give rise to the large number of different hematopoietic cell types which circulate in the blood. Most of the red and white cells in the blood are short-lived and need to be replaced constantly throughout life. The process of blood formation is normally maintained in the bone-marrow at a high rate. The levels of mature cells in the circulation can change rapidly in response to different environmental stress ranging from blood loss, infections, etc.
The normal hematopoiesis is based on the dual functioning of a small population of multipotential stem cells. This is based on an extensive self-generating capacity which gives rise to new undifferentiated stem cells and on the ability of the stem cells to differentiate into the various cell lineages through multiple maturation stages giving rise to committed cells with limited capacity for cell division. The two main lines of differentiation from stems cells are the lymphoid lineage and the myeloid lineage.
The growth factors produced by the stromal cells located in the bone marrow regulate the number of self-replication multipotential stem cells. The division and differentiation of the committed cells is dependent on the continuous supply of specific glycoproteins regulating each of the hematopoietic lineages.
The myeloid lineage is controlled by a group of glycoproteins called colony stimulating factors (CSFs). In the murine system, four types of CSF were identified: multi-CSF (IL-3) exerts its effect on undifferentiated stem cells on precursors of granulocytes, macrophages, megakoryocytes, erythroid cells and in addition on basophils and mast cells. GM-CSF is a proliferative factor for macrophages eosinophils, neutrophils and also for megakaryocytes and erythroid cells in the presence of erythropoietin, G-CSF and M-CSF exert their effect on committed granulocytes, later in the maturation sequence.
Erythroid cells are controlled by burst promoting activity (BPA) in the earlier stages and by erythropoietin at the later stages of differentiation.
The megakaryocytic lineage is controlled by at least two factors: megakaryocytic colony stimulating activity (Meg - CSA) and thrombopoietin which regulates the early and more mature stages of the megakaryocytes respectively.
The lymphoid lineage gives rise to lymphoid progenitor with the potential to differentiate into either T or B cells. Precursors of T lymphocytes migrate to the thymus and become immunocompetent under the influences of thymic hormones. Then the T lymphocytes migrate to the lymphoid tissues where their activity is regulated by the T cell growth factor.
The process of hematopoiesis may be adversely affected by different diseases or by adverse environmental factors such as radiation.
Bone marrow transplants are used to provide a host with a healthy stem-cell population that is capable of differentiation into mature blood cells that will replace the hematopoietic cells of the host suffering from immunodeficiency syndromes, aplastic anemias and leukemias. Other indications for bone marrow transplants include hemoglobinopathies such as thalassemia and accidental exposure to high levels of radiation and chemotherapeutic treatments.
The marrow is obtained from a donor and may be incubated with monoclonal antibodies to T-lymphocytes prior to transplantation for the purpose of preventing graft versus host disease. Generally, no adjuvant is given in combination with the bone marrow transplant. The number of donors who match the recipients who require transplants is inadequate to meet the demand.
When a bone marrow transplant is carried out, from 3 to 5% of the bone marrow cells must be taken from the donor in order to provide the donee with a sufficient amount of cells that will establish a stem cell producing capability in the recipient. The scarcity of suitable donors limits the number of bone marrow transplants that may be carried out.